Melatonin is a hormone that is secreted by the pineal gland in response to sunlight.

In addition to its effects on diurnal rhythms in mammals, it has been shown in vitro to inhibit melanogenesis in a dose-related manner. Topically applied melatonin has a clear-cut protective effect against UV-induced erythema.

It was found that it did not affect tyrosinase activity, suggesting that its effect occurs more proximally in the melanogenesis pathway. Free radical scavenging of UV-generated hydroxyl radicals and interference with the arachidonic acid metabolism are possible mechanisms of the melatonin action. Melatonin has been shown to inhibit cyclic AMP-driven processes in pigment cells.

The concentration needed for effective depigmentation in human skin has not yet been established, but a melatonin dosage of 0.6 mg/ cm2 has been shown to have antiinflammatory activity.

The effects of melatonin, N-acetylserotonin and serotonin on the growth and tyrosinase activity of SKMel 23 and SK-Mel 28 human melanoma cell lines were investigated. It was found that the growth and tyrosinase activity of SK-Mel 23 cells were not affected by melatonin or its precursors. These cell lines possess high affinity binding sites, which may be non-functional, or trigger responses other than those investigated herein.